Our aim is to develop a simple and effective method for the delivery of flu vaccines by noninvasive application of genetic vectors onto the skin. the hypothesis is that the expression of viral-specific antigens in the outer layer of skin can induce systemic immune responses against the influenza A virus. We have demonstrated that animals could be vaccinated by noninvasive application of adenovirus recombinants encoding specific antigens onto the skin. These studies will further develop skin-targeted noninvasive vaccines, and specifically determine whether this novel approach for the delivery of vaccines can mobilize the immune repertoire toward a beneficial immune protection against the influenza A virus. In this project, noninvasive vaccination onto the skin (NIVS) will be refined by formulating a new generation of adenovirus vectors of DNA/adenovirus complexes into skin-targeted noninvasive vaccines against the influenza nuclear protein and hemagglutinin. Efficacy of NIVS will be compared with those induced by other means. The overall goal of these experiments is to determine whether flu vaccines can be effectively delivered by noninvasive application of genetic vectors onto the skin that requires a lower level of skill in a needle-free manner. PROPOSED COMMERCIAL APPLICATION: Noninvasive vaccination onto the skin may boost vaccination rates against flu because the procedure is simple, effective, painless, and potentially safe. The development may also make vaccination programs less dependent upon medical resources.